7-17330557-A-T

Variant names:

• chr7-17330557-A-T
• rs3802082
• NM_001621.5:c.575-199A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001621.5(AHR):​c.575-199A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 151,936 control chromosomes in the GnomAD database, including 2,505 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (2505 hom., cov: 32)
• Consequence: AHR NM_001621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300
• Publications: 5 publications found

Genes affected

AHR (HGNC:348): (aryl hydrocarbon receptor) The protein encoded by this gene is a ligand-activated helix-loop-helix transcription factor involved in the regulation of biological responses to planar aromatic hydrocarbons. This receptor has been shown to regulate xenobiotic-metabolizing enzymes such as cytochrome P450. Before ligand binding, the encoded protein is sequestered in the cytoplasm; upon ligand binding, this protein moves to the nucleus and stimulates transcription of target genes. [provided by RefSeq, Sep 2015]

AHR Gene-Disease associations (from GenCC):

• retinitis pigmentosa 85

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• foveal hypoplasia

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000283321 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHR	NM_001621.5	c.575-199A>T		intron_variant	Intron 5 of 10	ENST00000242057.9	NP_001612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHR	ENST00000242057.9	c.575-199A>T		intron_variant	Intron 5 of 10	1	NM_001621.5	ENSP00000242057.4
ENSG00000283321	ENST00000637807.1	c.545-199A>T		intron_variant	Intron 5 of 11	5		ENSP00000490530.1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26774 AN: 151818 Hom.: 2507 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.181

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.176 AC: 26782 AN: 151936 Hom.: 2505 Cov.: 32 AF XY: 0.177 AC XY: 13157 AN XY: 74290

African (AFR) AF: 0.167 AC: 6918 AN: 41508

American (AMR) AF: 0.163 AC: 2483 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 547 AN: 3470

East Asian (EAS) AF: 0.391 AC: 2021 AN: 5172

South Asian (SAS) AF: 0.174 AC: 839 AN: 4826

European-Finnish (FIN) AF: 0.158 AC: 1680 AN: 10600

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11765 AN: 67818

Other (OTH) AF: 0.179 AC: 378 AN: 2110

Alfa AF: 0.0726 Hom.: 78

Bravo AF: 0.179

Asia WGS AF: 0.225 AC: 780 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.065
DANN	Benign	0.074
PhyloP100		-0.0030
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3802082; hg19: chr7-17370181;